Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction
van Breda S.G.J. et al.
Valproic acid (VPA) is a very potent anti-cancer and neuro-protective drug probably by its HDAC inhibiting properties, which may cause steatosis in the liver. The present study investigates the effect of repetitive VPA treatment of primary human hepatocytes (PHH) on whole genome gene expression-, DNA methylation-, a...
Copper induces expression and methylation changes of early development genes in Crassostrea gigas embryos
Rossana Sussarellu, Morgane Lebreton, Julien Rouxel, Farida Akcha, Guillaume Rivière
Copper contamination is widespread along coastal areas and exerts adverse effects on marine organisms such as mollusks. In the Pacific oyster, copper induces severe developmental abnormalities during early life stages; however, the underlying molecular mechanisms are largely unknown. This study aims to better unders...
Genome-wide analysis of day/night DNA methylation differences in Populus nigra.
Ding C.J. et al.
DNA methylation is an important mechanism of epigenetic modification. Methylation changes during stress responses and developmental processes have been well studied; however, their role in plant adaptation to the day/night cycle is poorly understood. In this study, we detected global methylation patterns in leaves o...
Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci
Bell C.G. et al.
Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly encoding the DNA methylome. Therefore, genetic polymorphism impacts on ...
Data on novel DNA methylation changes induced by valproic acid in human hepatocytes
Wolters J. et al.
Valproic acid (VPA) is a widely prescribed antiepileptic drug in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis. However the exact mechanism of the steatosis formation is unknown. The data presented in this DIB publication is used to further investigate the VPA-induced m...
Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes
Wolters J.E.J. et al.
Valproic acid (VPA) is one of the most widely prescribed antiepileptic drugs in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis through mitochondrial dysfunction. The aim of this study is to further investigate VPA-induced mechanisms of steatosis by analyzing changes in p...
Genome methylation and regulatory functions for hypoxic adaptation in Tibetan chicken embryos
Zhang Y. et al.
Tibetan chickens have unique adaptations to the extreme high-altitude environment that they inhabit. Epigenetic DNA methylation affects many biological processes, including hypoxic adaptation; however, the regulatory genes for DNA methylation in hypoxic adaptation remain unknown. In this study, methylated DNA immuno...
Emerging Role of One-Carbon Metabolism and DNA Methylation Enrichment on δ-Containing GABAA Receptor Expression in the Cerebellum of Subjects with Alcohol Use Disorders (AUD
Gatta E. et al.
Cerebellum is an area of the brain particularly sensitive to the effects of acute and chronic alcohol consumption. Alcohol exposure decreases cerebellar Purkinje cell output by increasing GABA release from Golgi cells onto extrasynaptic α6/δ-containing GABAA receptors located on glutamate...
Coordinate Regulation of TET2 and EBNA2 Control DNA Methylation State of Latent Epstein-Barr Virus
Lu F. et al.
Epstein-Barr Virus (EBV) latency and its associated carcinogenesis are regulated by dynamic changes in DNA methylation of both virus and host genomes. We show here that the Ten-Eleven Translocation 2 (TET2) gene, implicated in hydroxymethylation and active DNA demethylation, is a key regulator of EBV latency type DN...
Intracellular adenosine regulates epigenetic programming in endothelial cells to promote angiogenesis
Xu Y. et al.
The nucleoside adenosine is a potent regulator of vascular homeostasis, but it remains unclear how expression or function of the adenosine-metabolizing enzyme adenosine kinase (ADK) and the intracellular adenosine levels influence angiogenesis. We show here that hypoxia lowered the expression of ADK and increased th...
Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b
Kevin T. Ebata, Kathryn Mesh, Shichong Liu, Misha Bilenky, Alexander Fekete, Michael G. Acker, Martin Hirst, Benjamin A. Garcia and Miguel Ramalho-Santos
Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA...
Dynamics of DNA methylomes underlie oyster development
Riviere G. et al.
DNA methylation is a critical epigenetic regulator of development in mammals and social insects, but its significance in development outside these groups is not understood. Here we investigated the genome-wide dynamics of DNA methylation in a mollusc model, the oyster Crassostrea gigas, from the egg to the completio...
MeDIP-seq and nCpG analyses illuminate sexually dimorphic methylation of gonadal development genes with high historic methylation in turtle hatchlings with temperature-dependent sex determination
Radhakrishnan S. et al.
DNA methylation alters gene expression but not DNA sequence and mediates some cases of phenotypic plasticity. Temperature-dependent sex determination (TSD) epitomizes phenotypic plasticity where environmental temperature drives embryonic sexual fate, as occurs commonly in turtles. Importantly, the temp...
Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice.
Al-Quraishy S. et al.
Epigenetic mechanisms such as DNA methylation are increasingly recognized to be critical for vaccination efficacy and outcome of different infectious diseases, but corresponding information is scarcely available for host defense against malaria. In the experimental blood-stage malaria Plasmodium chabaudi, we investi...
Comparative analysis of MBD-seq and MeDIP-seq and estimation of gene expression changes in a rodent model of schizophrenia
Neary J.L. et al.
We conducted a comparative study of multiplexed affinity enrichment sequence methodologies (MBD-seq and MeDIP-seq) in a rodent model of schizophrenia, induced by in utero methylazoxymethanol acetate (MAM) exposure. We also examined related gene expression changes using a pooled sample approach. MBD-seq and MeDIP-seq...
Overexpression of LINE-1 Retrotransposons in Autism Brain
Shpyleva S. et al.
Long interspersed nuclear elements-1 (LINE-1 or L1) are mobile DNA sequences that are capable of duplication and insertion (retrotransposition) within the genome. Recently, retrotransposition of L1 was shown to occur within human brain leading to somatic mosaicism in hippocampus and cerebellum. Because unregulated L...
Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis
Wolters J.E. et al.
Cyclosporine A (CsA) is an undecapeptide with strong immunosuppressant activities and is used a lot after organ transplantation. Furthermore, it may induce cholestasis in the liver. In general, the drug-induced cholestasis (DIC) pathway includes genes involved in the uptake, synthesis, conjugation, and secretion of ...
Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity
Keller M. et al.
DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individ...
Novel regional age-associated DNA methylation changes within human common disease-associated loci
Bell CG et al.
Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci.
In a discovery set of 2238 peripheral-blood genome-wide DNA methylomes aged 1...
Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing
Amabile A. et al.
Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently...
Trichloroethylene-Induced DNA Methylation Changes in Male F344 Rat Liver
Jiang Y. et al.
Trichloroethylene (TCE), a common environmental contaminant, causes hepatocellular carcinoma in mice but not in rats. To understand the mechanisms of the species-specific hepatocarcinogenecity of TCE, we examined the methylation status of DNA in the liver of rats exposed to TCE at 0 or 1000 mg/kg b.w. for 5 days usi...
Dynamic Interplay between the Transcriptome and Methylome in Response to Oxidative and Alkylating Stress
Deferme L et al.
In recent years, it has been shown that free radicals not only react directly with DNA but also regulate epigenetic processes such as DNA methylation, which may be relevant within the context of, for example, tumorigenesis. However, how these free radicals impact the epigenome remains unclear. We therefore investiga...
Efficiency of methylated DNA immunoprecipitation bisulphite sequencing for whole-genome DNA methylation analysis
Jeong HM et al.
We compared four common methods for measuring DNA methylation levels and recommended the most efficient method in terms of cost and coverage.
MATERIALS & METHODS:
The DNA methylation status of liver and stomach tissues was profiled using four different methods, whole-genome bisulphite sequencing (WG-BS), targe...
Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma
Linda Rieswijka, Sandra M.H. Claessena, Otto Bekersc, Marcel van Herwijnena, Daniël H.J. Theunissena, Danyel G.J. Jennena, Theo M.C.M. de Koka, Jos C.S. Kleinjansa,Simone G.J. van Bredaa
Chronic exposure to aflatoxin B1 (AFB1) has, in certain regions in the world, been strongly associated with hepatocellular carcinoma (HCC) development. AFB1 is a very potent hepatotoxic and carcinogenic mycotoxin which is frequently reported as a food contaminant. Epigenetic modifications provoked by environmental e...
Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring
Sabet JA, Park LK, Iyer LK, Tai AK, Koh GY, Pfalzer AC, Parnell LD, Mason JB, Liu Z, Byun AJ, Crott JW
The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.
In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intest...
Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through
Batista L et al.
The miR-200 family members have been implicated in stress responses and ovarian tumorigenesis. Here, we find that miR-200c/141 transcription is intimately linked to the transcription of the proximal upstream gene PTPN6 (SHP1) in all physiological conditions tested. PTPN6 and miR-200c/141 are transcriptionally co-reg...
Maternal immune activation induces GAD1 and GAD2 promoter remodeling in the offspring prefrontal cortex
Labouesse MA et al.
Maternal infection during pregnancy increases the risk of neurodevelopmental disorders in the offspring. In addition to its influence on other neuronal systems, this early-life environmental adversity has been shown to negatively affect cortical γ-aminobutyric acid (GABA) functions in adult life, including imp...
DNA methylation profiling: comparison of genome-wide sequencing methods and the Infinium Human Methylation 450 Bead Chip
Walker DL, Bhagwate AV, Baheti S, Smalley RL, Hilker CA, Sun Z, Cunningham JM
To compare the performance of four sequence-based and one microarray methods for DNA methylation profiling.
DNA from two cell lines were profiled by reduced representation bisulfite sequencing, methyl capture sequencing (SS-Meth Seq), NimbleGen SeqCapEpi CpGiant(Nimblegen MethSeq), methylated DNA...
Evidence for Epigenetic Regulation of Pro-Inflammatory Cytokines, Interleukin-12 and Interferon Gamma, in Peripheral Blood Mononuclear Cells from PTSD Patients
Marpe Bam, Xiaoming Yang, Juhua Zhou, Jay P. Ginsberg, Quinne Leyden, Prakash S. Nagarkatti, Mitzi Nagarkatti
While Post Traumatic Stress Disorder (PTSD) is associated with immune dysfunction, the underlying mechanisms remain unclear. Studies suggest a role for involvement of epigenetic mechanisms and microRNAs (miRNAs). Here, we examined genome-wide histone and DNA methylation in the peripheral blood mononuclear cells (PBM...
Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure
Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hep...
High cortisol in 5-year-old children causes loss of DNA methylation in SINE retrotransposons: a possible role for ZNF263 in stress-related diseases
Nätt D, Johansson I, Faresjö T, Ludvigsson J, Thorsell A
Childhood stress leads to increased risk of many adult diseases, such as major depression and cardiovascular disease. Studies show that adults with experienced childhood stress have specific epigenetic changes, but to understand the pathways that lead to disease, we also need to study the epigenetic l...
Arterial endothelial methylome: differential DNA methylation in athero-susceptible disturbed flow regions in vivo
Jiang YZ1, Manduchi E2, Stoeckert CJ Jr3, Davies PF
Atherosclerosis is a heterogeneously distributed disease of arteries in which the endothelium plays an important central role. Spatial transcriptome profiling of endothelium in pre-lesional arteries has demonstrated differential phenotypes primed for athero-susceptibility at hemodynamic sites associat...